Father's Day and Vasopressors

First of all, Happy Father's Day to all the dads out there!  Especially to my father, who taught by example what it means to be a man, and who's been nothing but supportive about my career choices and directions.  But enough of that stuff....I'll be calling him this evening :)

In the last post I shared some interesting research I found about using inotropes and vasopressors to treat shock; from that study (incidentally probably some of the best in terms of methodology and sample size), it seems that norepinephrine (a vasopressor) works AT LEAST as well as dopamine (inotrope) in most kinds of shock, and shockingly (ooh, that was a bad pun!) works better in cardiogenic shock.

How can this be?

I found, while messing around online, a great video from the SMACC (Social Media and Critical Care) 2013 conference.  In it, John Myburgh takes a look at the published evidence surrounding various adrenergic agents.  He spent a good deal of time talking about the fact that epinephrine and norepinephrine (or adrenaline and noradrenaline) are molecules inherent to the body, as opposed to things like dobutamine and milrinone.  But I still couldn't wrap my head around why a drug like epi nor norepi, which increases vascular resistance, is less damaging to patients with cardiovascular problems.  And then the lightbulb went off.

(Incidentally, I posted a link to the SMACC video on the Socratic Medic Facebook page.  You have "Like"d it, right?????)

My feeling is that a lot of clinicians, like me, equate "vascular resistance" with arterial vasomotor tone.  That's where the impossibility seems to lie; the heart has to work against greater pressures, which can't be good for the sick heart!  However, "vascular resistance" means much more than arterial tone; it means venous tone as well.  And there lies the answer!

(unfortunately, I can't remember from which website I got this picture.  No copyright infringement is intended!)

There are a couple of things that need to be pointed out:
1)  Perfusion (pressurized flow) depends on two things; pressure and volume.  Different types of blood vessels optimize those two factors.  Arteries, due to their thick walls, have much more to do with pressure than do veins.  As the circled area shows, almost three-quarters of your blood volume is located in the veins at any one time!
2)  The thick walls of the arteries resist dilation much better than the veins do.  Veins have such a tendency to dilate at normal physiology, in fact, that the legs of the muscles act as a "venous pump" to help ensure return of blood to the heart.

All very interesting, but why does a vasopressor improve cardiac output when it really shouldn't, based on increased vascular resistance and an ineffective pump?

Keep in mind, veins get innervated by sympathetic nerves too.  Increasing sympathetic stimulation will cause the veins to constrict, in addition to the arteries.  So what happens when veins constrict?  Pressure increases; the vein walls are more resistant to dilation, and one-way valves in the veins keep blood from backflowing.  So the blood can't go backwards, can't go sideways; it must go forward.

And preload increases.  Since preload increases, stroke volume increases, and the Frank-Starling law behaves as it always does.

CO = SV x HR

What about dopamine?

Dopamine is an inotrope; it increases activity at beta-1 receptors in the heart.  The result is that heart rate and contractility both increase.  But where's the fluid for the heart to pump?  The heart is a positive pressure pump; it can't suck blood in to the ventricles.  Increasing the heart rate and pumping strength without increasing the delivery of blood to the heart (through the veins) isn't a good solution.  It makes sense, then, that adding dopamine (or other inotropes) to increase pumping ability without first assuring adequate preload (with fluid boluses and/or vasopressors) doesn't improve outcomes.  And it also might give insight into why dopamine has so many adverse events like arrhythmias; increase the myocardial oxygen demand without increasing the oxygen supply, and what do you get???

Vasopressors do not just affect the arteries; they affect the veins as well.  Inotropes affect the heart.  If you increase the heart's pumping effectiveness, you'd better also have given it more blood to pump; venous vasoconstriction offers that.  Misuse the drugs on your ambulance at your patient's peril.